Active agents (for example, therapeutic agents such as drugs or immunologically active agents such as vaccines) are conventionally administered either orally or by injection. However, many active agents are completely ineffective or have radically reduced efficacy when orally administered since they either are not absorbed or are adversely affected before entering the bloodstream and thus do not possess the desired activity. On the other hand, the direct injection of active agents intravenously or subcutaneously, while assuring no modification of the agents during administration, can be invasive, painful, and often results in poor patient compliance.
Transdermal delivery of active agents, however, result in systemic circulation of the active agent and can provide an alternative mode of administration. For example, transdermal delivery can potentially provide better drug bioavailability than oral administration, in part because such delivery bypasses not only the initial metabolism of the drug by the liver and the intestines but also the unpredictable absorption of the drug from the gastrointestinal tract. Transdermal delivery also can result in more stable blood serum level of the drug (e.g., leading to a prolonged pharmacological effect that is similar to intravenous infusion), and can allow for easily adjustable dosing rate. For example, transdermal patches can be easily removed which results in rapid cessation of dosing and elimination of the drug from circulation. Finally, transdermal delivery typically results in greater patient compliance because it is non-invasive and can be easily administered.
The skin serves as a barrier to the penetration of many foreign substances. The feasibility of using transdermal delivery of active agents as a route of administration requires that a therapeutic rate of drug delivery through the skin be achieved. This can be accomplished if the skin can be made more permeable to the drug. Factors which determine the permeability of the skin to a particular drug can include drug diffusivity through the skin membrane and/or drug concentration in the vehicle. In addition, certain materials used as adjuvants in vehicles may affect the characteristics of the skin membrane barrier and thus alter the permeability of the skin to the drug. Permeation enhancers, for example, can maximize penetration rates and/or minimize lag times in drug penetration through the skin, and should be substantially non-toxic, non-irritant and non-sensitizing on repeated exposure.
However, it is often difficult to predict which compounds will work as permeation enhancers and which permeation enhancers will work for particular drugs. Consequently, there remains a need for transdermal formulations that could deliver, at controlled rates, an active agent or a mixture thereof, combined with appropriate permeation enhancers.